Walker 256乳腺癌细胞构建大鼠胫骨骨癌痛模型

目的: 探讨以Walker 256大鼠乳腺癌腹水瘤细胞制备大鼠胫骨骨癌痛模型，为骨癌痛机制和治疗研究提供有用的工具。方法：以Walker 256乳腺癌细胞接种幼年雌性SD鼠腹腔制备腹水瘤细胞，将15 μl腹水瘤细胞注入雌性成年SD鼠左侧胫骨骨髓腔制备骨癌痛模型；以注射加热灭活瘤细胞的     

华蟾素对骨癌痛大鼠的镇痛效应及对脊髓胶质细胞活化的影响

目的：探讨华蟾素对骨癌痛大鼠的镇痛效应及对脊髓胶质细胞活化的影响。方法：选用雌性SD大鼠48只,随机分为正常对照组、假手术组（胫骨内注射20 μL PBS）、模型组和华蟾素干预组,每组12只。模型组与华蟾素干预组大鼠胫骨内注射20 μL Walker 256乳腺癌细胞构建骨癌痛模型。华蟾素干预组于造模第7天开始腹腔注射华蟾素注射液,其余各组每天予以等量生理盐水,各组于造模前以及造模后第2、5、7、9、13、15天分别测定热缩足阈值和机械缩足阈值,造模第7天行胫骨X线摄片观察骨质破坏程度,末次行为学检测后处死大鼠,取外周血、L4～L6节段脊髓,利用免疫组化检测星形胶质细胞标记物（GFAP）和小胶质细胞标记物（Iba-1）的表达情况,ELISA检测外周血及脊髓中相关炎性因子（TNF-α和IL-1β）的表达。结果：X线显示模型组大鼠胫骨骨皮质破坏明显、骨质连续性缺乏、骨组织肿胀明显,正常对照组、假手术组未见明显骨组织肿胀、骨连续性较好,提示造模成功。行为学检测结果表明与模型组比较,华蟾素干预可明显缓解骨癌所诱发的机械痛敏、热痛敏（P < 0.01）。免疫组化结果提示与假手术组相比,模型组大鼠脊髓胶质细胞活化明显增强（P < 0.05）;与模型组相比,华蟾素能显著抑制脊髓胶质细胞活化（P < 0.05）。ELISA检测结果显示与假手术组相比,模型组大鼠脊髓及血清中TNF-α和IL-1β表达增强（P < 0.05）;与模型组相比,华蟾素能降低TNF-α和IL-1β表达（P < 0.05）。结论：华蟾素对骨癌痛大鼠有较好的镇痛效应,其镇痛作用可能是通过抑制脊髓星形胶质细胞及小胶质细胞活化发挥作用的。     

大鼠骨癌痛模型的建立及组织学研究

目的建立一个有用的癌痛动物模型.方法将MRMT-1大鼠乳腺癌细胞接种到SD大鼠胫骨上段骨髓腔内,造成骨癌痛动物模型.用von Frey细丝刺激足底和后肢负重测量仪分别测量机械性痛觉超敏和痛觉过敏,放射学方法评估骨破坏,同时,组织切片镜下观察肿瘤和骨结构的破坏情况.结果造模动物在14天左右开始出现机械性痛觉超敏和痛觉过敏,胫骨X线摄片显示明显的骨破坏,组织学研究显示骨髓腔内肿瘤生长,向外侵蚀破坏骨皮质,同时伴有新生的编织骨形成.结论从疼痛行为学、放射学、组织学多方面研究的结果,表明大鼠骨癌痛模型已复制成功.该癌痛模型的建立,将为我国癌痛新药的评价,尤其是研究治疗癌痛中药的疗效及作用机制提供一个有用的工具.     

P物质和降钙素基因相关肽在骨癌痛-吗啡耐受模型中的表达

背景与目的:多数晚期癌症患者会经历中重度癌痛折磨。阿片药物是癌痛治疗最常用和最有效的药物,但长时间使用容易造成耐受甚至痛觉过敏。P物质(substance P,SP)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)是疼痛信号传递中最重要的神经递质,但在癌痛-阿片耐受中的表达尚不清楚。本研究拟在骨癌痛-吗啡耐受大鼠模型上,探讨SP和CGRP在背根神经节(dorsal root ganglion,DRG)水平的表达特点。方法:60只Wistar大鼠鞘内置管成功后,随机分为3组:假手术组、吗啡耐受组和骨癌痛-吗啡耐受组。吗啡耐受组和骨癌痛-吗啡耐受组分别以热灭活Walker256乳腺癌细胞和Walker256乳腺癌细胞制备胫骨癌痛模型,接种后10 d时鞘内注射吗啡20μg/kg。动物行为学测试使用Von Frey纤维丝,于不同时间点测定机械刺激引起的机械缩足阈值。研究结束时,免疫组织化学分析DGR中SP和CGRP的表达,测定积分光密度IOD值。结果:行为学证实,吗啡耐受组和骨癌痛-吗啡耐受组在吗啡治疗第5天时出现耐受,骨癌痛-吗啡耐受组缩足阈值较吗啡耐受组和对照组明显降低(P<0.001)。骨癌痛-吗啡耐受组SP和CGRP积分光密度值IOD(9 917.9±2 246.1和15 021.5±2 989.7)较吗啡耐受组(5 191.7±1 052.6和9 737.1±2 239.8)和对照组(4 821.6±843.1和8 180.3±1 242.2)明显增加(P<0.001)。结论:SP和CGRP在癌痛-吗啡耐受大鼠模型DRG中表达增强,提示这两种神经递质参与了耐受产生,这将为新药治疗癌痛-吗啡耐受提供更符合临床的科学依据。     

大麻素受体2在胫骨癌痛大鼠脊髓背角细胞中的表达

目的：观察胫骨癌痛大鼠脊髓大麻素受体2（CB2）表达的变化,探讨CB2在骨癌痛中作用及其可能的脊髓机制。方法：雌性SD大鼠56只,体重160-180g,随机分为7组（n=8）：对照组、假手术组、骨癌痛组,假手术组和骨癌痛组又各分为3个亚组（术后7d、14d和21d组）,分别用免疫印迹法检测各组大鼠脊髓水平CB2表达的变化,激光共聚焦技术观察CB2的表达部位。结果：免疫印迹结果显示对照组基本没有CB2的表达,与对照组相比,假手术组及骨癌痛组脊髓CB2表达水平升高（P〈0.05）;与假手术组相比,骨癌痛7d组脊髓CB2蛋白表达明显上调（P〈0.05）。激光共聚焦技术显示CB2主要表达于脊髓小胶质细胞和星形胶质细胞。结论：胫骨癌痛大鼠脊髓背角有CB2表达,早期为其表达的高峰,且主要表达于小胶质细胞和星形胶质细胞。     

何首乌有效成分对大鼠骨癌痛的镇痛效果

目的  探讨何首乌有效成分对大鼠骨癌痛的镇痛作用。方法 将36只SPF级雌性SD大鼠随机分成3组：A组为正常空白对照（n=6），B组大鼠注射无菌生理盐水（n=6），C组大鼠左后腿胫骨注射乳腺癌细胞walker256建立骨癌痛模型（n=24）。建立骨癌痛模型的C组SD大鼠按灌胃药物随机分成C1、C2、C3、C4 4组，每组6只。建模成功后14 d、15 d、16 d连续对C1~C4组大鼠分别灌胃生理盐水（2 mL）、二苯乙烯苷（60 mg/mL，2 mL）、大黄素（60 mg/mL，2 mL）和儿茶素（60 mg/mL，2 mL）。每次灌胃前、灌胃后30 min、灌胃后1.0 h测量大鼠左脚掌的机械痛阈值。结果 癌痛模型喂养第5天起，与A、B两组比较，C组大鼠机械痛阈值降低（P<0.05），骨质明显破坏；A、B两组大鼠机械痛阈值无明显差异，骨质结构正常。C2组大鼠各时点的机械性痛阈值均较C1组、C3组、C4组明显增加（P<0.05）。与灌胃前比较，C2组大鼠模型灌胃30 min和灌胃后1 h后机械性痛阈值明显升高（P<0.05），但灌胃30 min和灌胃后1 h后的机械性痛阈值无统计学意义（P>0.05）。结论 何首乌可有效降低大鼠的骨癌痛，其有效单体成分是二苯乙烯苷。     

鞘内注射Quinpirole对骨癌痛大鼠镇痛及脊髓小胶质细胞活化的影响

目的 探讨鞘内注射Quinpirole（QNP）对骨癌痛大鼠镇痛及脊髓小胶质细胞活化的影响。方法 选取健康成年雄性SD大鼠60只通过胫骨骨髓腔内注射Walker256乳腺癌细胞液制备骨癌痛模型。将骨癌痛大鼠随机分为高剂量10μg/kg QNP（QNP-H）、低剂量5μg/kg QNP（QNP-L）及生理盐水（NS）3组,每组20只;QNP采用每日鞘内注射方式,注射体积为10μl。选取20只同周龄大鼠作对照（C）,NS组和C组仅给予等体积生理盐水。分别于治疗前、治疗1、3、5、7d后对各组进行行为学检测,分析以上观察时间点大鼠的机械缩足阈值（MWT）和缩足热潜伏期（WTL）;采用免疫组化法检测脊髓离子钙接头蛋白分子 1（Iba-1）染色以及特异表达补体C3受体（OX-42）和大麻素受体2（CB2）的荧光积分光密度（IOD）;酶联免疫吸附法检测脊髓肿瘤坏死因子（TNF）-α和白介素（IL）-1β水平;Western blotting检测脊髓Toll样受体-4（TLR-4）及受体-2（TLR-2）蛋白表达水平。结果 与C组相比,其余3组各观察时间点的MWT、WTL降低;Iba-1染色程度、OX-42和CB2的IOD、脊髓TNF-α和IL-1β水平、TLR-4和TLR-2水平均升高,差异均有统计学意义（P＜0.05）。在骨癌痛大鼠模型中,QNP-H组、QNP-L组在上述指标与NS组的差异均有统计学意义（P＜0.05）;且QNP-H组均优于QNP-L组（P＜0.05）。结论 鞘内注射QNP对骨癌痛大鼠有较好的镇痛作用,同时可降低脊髓小胶质细胞活化及炎症反应。     

应用MADB-106乳腺癌细胞构建大鼠转移性骨癌痛模型

目的应用MADB-106大鼠乳腺癌细胞构建转移性骨癌痛模型,通过对该模型痛行为学、影像学、组织学观察等检测进行治疗研究。方法将MADB-106大鼠乳腺癌细胞接种到SD大鼠胫骨上段骨髓腔内,构建骨癌痛动物模型。以大鼠自发性缩足反射次数评估大鼠自发性痛情况,以自由活动时下肢跛行程度评分观察大鼠行走诱发痛,以热痛觉阈值观察大鼠热痛觉过敏情况,以X线、骨组织病理学检测观察癌细胞对骨结构的破坏程度。结果造模组大鼠术后第15天自发缩足反射次数为（14．42±1．24）次,第22天为（18．33±1．37）次,第25天为（21．25±1．54）次,与术前比较差异有统计学意义（均P〈0．001）;术后第15天热刺激痛觉阈值为（11．86±1．63）S,第22天为（8．38±1．05）S,第25天为（7．47±1．25）s（P〈0．001）;术后第15天自由行走痛评分为（1．25±0．62）分,第22天为（2．00±0．95）分,第25天为（2．33±1．07）分。术后第15天开始出现明显的自发性痛、热痛觉过敏和行走诱发痛,胫骨X线片显示明显的骨破坏,组织学研究显示骨髓腔内肿瘤生长,向外侵蚀破坏骨皮质。结论成功应用MADB-106乳腺癌细胞构建大鼠骨癌痛模型,造模2周后可以用于癌痛治疗的评价。     

唑来膦酸不同给药方式对骨癌痛大鼠镇痛作用的比较

目的:通过对鞘内注射和皮下注射两种给药方式的比较,探讨唑来膦酸对骨癌痛大鼠的镇痛效应及其可能机制。方法:将Walker 256乳腺癌细胞注入雌性SD大鼠胫骨以建立骨癌痛模型,单次或者持续给予唑来膦酸后,比较鞘内和皮下两种给药方式对大鼠痛行为学的影响。采用RT-PCR、Western blot和免疫荧光染色的实验方法观察脊髓背角IBA-1的改变情况。采用旷场实验和转棒实验观察唑来膦酸两种给药方式对大鼠运动功能和自发活动功能的影响。结果:单次或连续鞘内或皮下注射唑来膦酸均可显著改善大鼠热痛敏反应（P<0.05）,并且鞘内注射的镇痛效应强于皮下注射（P<0.05）。RT-PCR、免疫荧光染色和Western blot结果表明,持续鞘内注射唑来膦酸7天后,骨癌痛大鼠脊髓背角表达增高的IBA-1被显著抑制（P<0.05）,而皮下注射并无此抑制效应（P>0.05）。唑来膦酸的两种给药方式均未影响大鼠的运动功能和自发活动功能（P>0.05）。结论:相比皮下注射,鞘内注射唑来膦酸在大鼠骨癌痛模型中表现出更强的镇痛效应,而抑制脊髓小胶质细胞的活化可能是其镇痛机制之一,此外,唑来膦酸在两种给药方式中均未表现出明显的神经毒副作用。     

乳腺癌MRMT-1细胞局部骨转移大鼠模型的研究

目的 研究乳腺癌MRMT-1细胞局部骨转移大鼠模型在痛觉反应、影像学、病理学和分子生物学等方面的表现,为进一步的发病机制和药理学研究提供资料.方法 将32只雌性SD大鼠用随机数字表法分为假手术组和模型组各16只,在模型组大鼠胫骨内注射乳腺癌MRMT-1细胞,引起局部骨转移.造模后19d测定痛觉反应,21d处死大鼠取材,测定肿瘤体积,用X线对骨质损伤进行评分并测定骨密度（BMD）,HE染色观察病理形态改变,抗酒石酸酸性磷酸酶（TRAP）法染色观察破骨细胞,免疫组织化学法检测核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）水平,并计算比值;实时荧光定量反转录聚合酶链反应（RT-PCR）法检测甲状旁腺激素相关蛋白（PTHrP）水平.结果 与假手术组比较,模型组存在痛觉异常状态（P＜0.01）;胫骨在X线下损伤评分较高（P＜0.01）.模型组和假手术组大鼠左侧胫骨的BMD分别为（0.11 ±0.01）g/cm2和（0.13±0.02）g/cm2（P＜ 0.05）.模型组胫骨标本上肿瘤生长明显,体积为（1082.73±679.44）mm3,而假手术组无肿瘤生长（P＜0.01）,病理可见混合性骨转移,但以溶骨性病变为主;伴有破骨细胞数量明显增多,达到（40.84±25.59）个/高倍视野,而假手术组仅为（1.88±2.92）个/高倍视野（P＜0.01）.转移灶局部RANKL水平无明显变化,OPG水平下降（P＜0.05）,OPG/RANKL比值和PTHrP下降（P＜0.05）.结论 乳腺癌MRMT-1细胞局部骨转移大鼠模型存在癌痛、骨质破坏,甚至病理性骨折等表现.其发病机制可能是MRMT-1细胞在浸润生长过程中打破了OPG-RANKL-RANK系统的平衡,从而激活破骨细胞,引起骨吸收作用亢进,引起各种表现.     

Achievement of personalized pain goal in cancer patients referred to a supportive care clinic at a comprehensive cancer center

BACKGROUND:

Cancer pain initiatives recommend using the personalized pain goal to tailor pain management. This study was conducted to examine the feasibility and stability of personalized pain goal, and how it compares to the clinical pain response criteria.

METHODS:

Records of 465 consecutive cancer patients seen in consultation at the Supportive Care Clinic were reviewed. Pain relief was assessed as clinical response (≥30% or ≥2 point pain reduction) and personalized pain goal response (pain ≤ personalized pain goal).

RESULTS:

One hundred fifty‐two (34%), 95 (21%), and 163 (37%) patients presented with mild (1‐4), moderate (5‐6), and severe (7‐10) pain, respectively. Median age (59 years), males (52%), and advanced cancer status (84%) did not differ by pain category. Median personalized pain goal at initial clinic consult was 3 (interquartile range, 2‐3), was similar across pain groups, and remained unchanged (P = .57) at follow‐up (median, 14 days). Clinical response was higher among patients with severe pain (60%) as compared with moderate (40%) and mild pain (33%, P < .001). Personalized pain goal response was higher among patients with mild pain (63%) as compared with moderate (44%) and severe pain (27%, P < .001). By using personalized pain goal response as the gold standard for pain relief, the sensitivity of clinical response was highest (98%) among patients with severe pain, but it had low specificity (54%). In patients with mild pain, clinical response was most specific for pain relief (98%), but had low sensitivity (52%).

CONCLUSIONS:

Personalized pain goal is a simple patient‐reported outcome for pain goals. The majority of patients were capable of stating their desired level for pain relief. The median personalized pain goal was 3, and it was highly stable at follow‐up assessment. Cancer 2012. © 2011 American Cancer Society.     

Assessment and measurement of pain

This paper provides an overview of issues relating to pain assessment and management. Areas to be covered include the problems involved in assessing pain as a subjective phenomenon, the constraints of assessment within the clinical field, factors that affect pain, and pain assessment tools and questionnaires. The aim of the reference list is to provide back-up reading to assist in exploring the options available when considering the possibility of compiling a pain assessment protocol for individual clinical areas.     

Wider issues in pain management

In this paper the accepted holistic approach to pain management in cancer care is scrutinized. A series of oppositions are considered to result from the essential indeterminate nature of pain, and that pain is fundamentally lived and experienced in the body. These oppositions are discussed in terms of mind-body dualism and embodiment, and in particular the body as subject and object. The discussion is illustrated with examples from research examining individual expressions of pain. Patients'powerful attempts to manipulate subject-object distinctions in recounting their experience of pain is offered as a means by which patients make sense of their pain, and connect it to their bodies and to their identity. The implications of acknowledging personal and cultural meanings attributed to pain are highlighted, with recommendations for future research and clinical practice initiatives.     

Patients' and nurses' assessment of cancer pain

The purpose of this study was to examine hospitalised cancer patients' and nurses' assessment of patients' cancer pain and to compare them. The data were collected from 51 patient–nurse pairs in two hospitals from oncological and medical clinics. Each nurse and patient took part in the study no more than once. The data were collected with a structured interview and the questionnaire. The intensity of pain was measured with a visual analogue scale (VAS) and the Finnish version of the McGill Pain Questionnaire (FPQ). The results showed that the differences between patients' and nurses' assessments were statistically significant for most intensive pain and for acceptable pain. In both cases nurses' assessments of the intensity of pain were lower than patients' assessments. The nurses identified 40 words in the verbal FPQ that the patients used in describing their experiences of pain. The words used most often by patients were agonizing, tender, wave-like and radiant. The word that the nurses used most often was that of intense. Nurses' knowledge about pain medication in general and morphine in particular was clearly associated with the differences observed in estimates of the intensity of pain. Nurses with poor knowledge underestimated the patients' most intensive experiences of pain. The difference was statistically significant.     

慢性顽固疼痛患者芬太尼透皮贴剂的门诊治疗

目的:观察门诊慢性疼痛患者用芬太尼透皮贴剂(Transdermalfentanyl,TDF)的镇痛疗效。方法:选择慢性顽固性疼痛患者416例,其中中、晚期癌症性疼痛占314例,非癌性疼痛102例,使用TDF止痛。对治疗前后的疼痛强度、生活质量评价及用药中的不良反应,进行观察和统计分析。结果:癌性疼痛治疗前疼痛视觉模拟评分(VAS)为7.94±1.15,治疗后降低至1.64±1.71;非癌性疼痛治疗前为7.30±1.54,治疗后降低至1.91±1.53。癌性疼痛的明显缓解率为51.5%,完全缓解为19.7%,总缓解率71.2%。非癌性疼痛明显缓解率为45.0%,完全缓解13.7%,总缓解率58.7%。生活质量治疗前后均变化(P<0.01)。用药的不良反应与传统的阿片类药物相似,为便秘、恶心、呕吐、头晕等症,但程度较轻;未出现呼吸抑制者。治疗后需停药的患者无身体及精神戒断症状发生。结论:TDF具有无创性、不间断的给药途径,镇痛效果确实,不良反应发生率低,患者依从性好,适合门诊、家庭应用。     

Cancer pain assessment – Can we predict the need for specialist input?

We can anticipate that failure to assess cancer pain adequately will inevitably lead to inappropriate application of pain management options. However, it is not always standard practice to teach the limitations of the question ‘How bad is the pain?’, as well as the need to consider what may complicate pain management or be a poor prognostic factor for pain control. These issues may complicate cancer pain assessment and require specialist consultation. An internationally accepted classification system for cancer pain could provide the basis for a multidimensional assessment and a common language for clinical and research work. Research dating back to the late 1980s has resulted in the development of the Edmonton Classification System for Cancer Pain. This includes many of the factors that may be prognostic for the complexity of cancer pain management and can assist an inexperienced clinician in anticipating the need for specialist advice.     

The Good Pain Management （GPM） Ward Program in China and its impact on Chinese cancer patients： the SYSUCC experience

To improve cancer pain management, trle MeCllCal uncology uepartmem of sun yat-sen University Cancer Center （SYSUCC） launched the Good Pain Management （GPM） Ward Program, which has been recognized by the Chinese Ministry of Health and promoted throughout the nation. This retrospective casecontrol study was designed to evaluate the effectiveness of the program. Patients diagnosed with malignant solid tumors with bone metastasis were eligible. Patients who were admitted 6 months before the initiation of the GPM program were used as the control group, and patients admitted 6 months after the initiation of the program were used as the GPM group. The painreporting rate and pain management index （PMI） were calculated. The pain levels before and after pain management were compared. A total of 475 patients （244 in the control group and 231 in the GPM group） were analyzed. The painreporting rate of the GPM group was significantly higher than that of the control group （62.8% vs. 37.7%, P 〈 0.001）. The PMI of the GPM group was significantly higher than that of the control group （0.083 vs. -0.261, P 〈 0.001）. Therefore, the GPM Ward Program improved the pain management of cancer patients and provided experience for improving cancer pain management in the future.